The Attitude Doc

Sept. 30, 2008 -- New discoveries about the genetic roots of gout may lead to new gout treatments and new tests to gauge a person's risk of developing gout.

Researchers including Abbas Dehghan, MD, of Erasmus Medical Center in the Netherlands report that news in tomorrow's online edition of The Lancet.

Dehghan's team studied gene data from three long-term health studies that together included more than 26,700 participants in the U.S. and the Netherlands.

The key findings:

• Two new gout genes. Gout and high uric acid concentration were linked to certain variations in the ABCG2 or SL17A3 genes.
• Another gout gene confirmed. The researchers confirmed that a variation in the SLC2A9 gene is linked to uric acid concentration and gout risk.
• Gout gene risk score. The researchers calculated participants' odds of having gout, based on how many of the gout gene variants they had.

Each gene variant, by itself, carried a "modest" risk of gout, but together, those variants drove gout risk up higher. The findings held regardless of other factors that make gout more likely.

In their report, Dehghan and colleagues suggest that their genetic risk score might help predict who will develop gout. The researchers also write that the genes they identified "could be useful" in developing new drugs to improve gout treatment.

It's not clear if the genetic risk score will catch on, and scientists don't yet know exactly what the two new gout genes do, but the discoveries may lead to better understanding of gout, according to an editorial published with the study. The editorialists included Martin Aringer, MD, of Germany's Technical University of Dresden.

(What does gout look like? See WebMD's gout slide show.)

SOURCES:

Dehghan, A. The Lancet, Oct. 1, 2008; online edition.

Aringer, M. The Lancet, Oct. 1, 2008; online edition.

Sept. 30, 2008 - Results are in from a national study examining whether two popular supplements slow the progression of knee arthritis, but they are far from conclusive.

The supplements glucosamine and chondroitin sulfate, taken together or alone, failed to show a clear advantage over placebo as a treatment to slow the progression of osteoarthritis of the knee.

There was a suggestion that taking glucosamine alone might be beneficial, lead researcher Allen D. Sawitzke, MD, of the University of Utah School of Medicine, tells WebMD. But the two-year study was not large enough or long enough to show this.

"I would definitely not want the message from this study to be that these supplements don't work at all," he says. "That would be a disservice because they might prove valuable in future studies."

Glucosamine, Chondroitin Used by Millions

The latest findings are an extension of the National Institutes of Health-funded Glucosamine/chondroitin Arthritis Intervention Trial (GAIT).

In 2006, GAIT researchers reported that the supplements were not much better than placebo for reducing knee pain associated with osteoarthritis. Researchers followed close to 1,600 patients who took one or both of the supplements, the painkiller Celebrex, or placebo for six months.

Some benefit was seen in patients with moderate to severe pain who took both glucosamine and chondroitin, but the finding was not conclusive because only a small number of patients in the study had pain that was considered moderate to severe.

In an effort to determine if the supplements help slow the destruction of knee cartilage, 572 of the original GAIT participants continued to take their original study treatment for an additional 18 months. All these patients had moderate to severe osteoarthritis.

The researchers used a specific X-ray protocol to determine the rate of osteoarthritis progression over time.

After two years, there was no significant difference between treatment and placebo groups.

"While we found a trend toward improvement among those with milder osteoarthritis of the knee in those taking glucosamine alone, we were not able to draw any definite conclusions," Sawitzke says.

Interpretation of the results was also complicated by the fact that the placebo group had less arthritis progression during the two-year study than the researchers had predicted.

The X-ray protocol used to measure osteoarthritis progression also proved to be less than optimal, says Josephine Briggs, MD, who directs the NIH's National Center for Complementary and Alternative Medicine, which co-sponsored the study.

Briggs tells WebMD that better ways of measuring osteoarthritis progression may be on the horizon, including the use of MRI.

"To really understand the promise of these interventions our measures must be maximally sensitive," she says.

The latest GAIT findings appear in the October issue of the journal Arthritis & Rheumatism.

What Should Patients Do?

Roughly 21 million American have osteoarthritis. While many patients end up having surgery to replace worn-out knees, Sawitzke says there are few nonsurgical treatments that address disease progression.

"Right now we essentially have nothing to offer," he says.

He recommends that people who want to try one of the supplements use glucosamine alone rather than glucosamine and chondroitin because there is some evidence that glucosamine absorption is compromised with the combination treatment.

"I tell my patients who want to take it for pain to try it for a few weeks or a month," he says. "That should be long enough to tell if it is working for you."

The GAIT study and others suggest that glucosamine and chondroitin are safe supplements, but Briggs says patients who take them or any supplement should always discuss it with their doctor.

She says more than two out of three adults in the U.S. use some type of complementary or alternative medicine, but only about one in three tell their physicians about it.

"It is important to discuss any medication you take with your doctor, including complementary and alternative medicines," she says.

SOURCES:

Sawitzke, A.D., Arthritis & Rheumatism, October 2008; vol 58: pp 3183-3191.

Allen D. Sawitzke, MD, University of Utah School of Medicine, Salt Lake City.

Josephine P. Briggs, MD, director, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Md.

Sept. 30, 2008 -- Long-term psychodynamic psychotherapy (LTPP) is more effective than short-term therapy for patients with complex mental disorders such as personality disorders, according to a new report.

The report's authors, including Falk Leichsenring, DSc, of the University of Giessen in Germany and Sven Rabung, PhD, of the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, analyzed data from 23 existing studies, involving a total of 1,053 patients treated with long-term psychodynamic psychotherapy. In all the studies, LTPP lasted at least a year.

According to the American Psychiatric Association, psychodynamic psychotherapy is a "treatment to help patients understand themselves more fully. This approach may involve uncovering -- and learning to deal more effectively with -- unconscious conflicts. It may also involve assisting patients to understand how certain types of adverse childhood experiences have left them feeling incomplete, anxious, or plagued with low self-esteem that interferes with realistic adult functioning."

The report, published in The Journal of the American Medical Association, concluded that patients with complex mental disorders who completed LTPP were better off than 96% of patients in comparison groups. Complex mental disorders included personality disorders, chronic mental disorders lasting at least a year, complex depressive or anxiety disorders, or those with two or more mental disorders.

"In this meta-analysis, LTPP was significantly superior to shorter-term methods of psychotherapy with regard to overall outcome, target problems, and personality functioning," the study says.

In an accompanying editorial, Richard M. Glass, MD, deputy editor of The Journal of the American Medical Association, argues that LTPP is being used less these days, at least in part because it is not as cost-effective as medication with brief supportive visits.

"This trend appears to be strongly related to financial incentives and other pressures to minimize costs," he writes. "Is that what is really wanted for patients with disabling disorders that could respond to more intensive treatment?"

SOURCES:

Leichsenring, F. The Journal of the American Medical Association, Oct. 1, 2008; vol 300: pp 1551-1556.

Glass, R. The Journal of the American Medical Association, Oct. 1, 2008; vol 300: pp 1587-1589.

News release, The Journal of the American Medical Association.

American Psychiatric Association.

Sept. 30, 2008 -- A gene found only in fat cells is linked to colon cancer, researchers find.

The finding provides part of the answer to a big question: What triggers colon cancer?

To get at this question, Boris Pasche, MD, PhD, and colleagues followed a trail of clues that implicates adiponectin, a hormone made only by fat cells.

• Colon cancer cells have more adiponectin receptors than do normal gut cells.
• People with the highest adiponectin levels have a 47% lower risk of colon cancer than do people with the lowest adiponectin levels.
• Obese people have decreased adiponectin levels.
• Obese people have an increased risk of colon cancer.

The researchers looked at five common variants of the adiponectin gene and five common variants of the gene for the adiponectin receptor.

They first analyzed adiponectin genes from about 1,100 people of Ashkenazi Jewish ancestry, including 441 colon cancer patients. This population is at particularly high risk of colon cancer. Three adiponectin gene variants, and one adiponectin receptor gene variant, affected colon cancer risk.

The researchers then analyzed the same gene variants in 199 colon cancer patients and 199 matched controls in mixed-ethnicity Chicago-area residents. Only one variant of the adiponectin gene was linked to colon cancer, but it was the same as one of the variants in the first study and reduced the risk of colon cancer by the same amount.

When the studies were combined, the gene variant cut colon cancer by 27%.

"Now, for the first time, we see a gene in these fat cells is linked to colon cancer," Pasche says.

Evadnie Rampersaud, PhD, research assistant professor at the University of Miami's Institute for Human Genomics, says it's an important finding. Rampersaud was not involved in the Pasche study.

"What is unique is this is the first time anybody has identified a genetic variation, a location within the adiponectin gene, that they can link to colon cancer," Rampersaud tells WebMD. "That is pretty amazing."

What excites Pasche and Rampersaud isn't the specific gene variant linked to colon cancer. What's much more interesting is that this variant points to a specific region of the adiponectin gene that affects colon cancer -- and, very likely, other types of cancer as well.

"This opens the door for more research," Pasche says.

Pasche and colleagues report their findings in the Oct. 1 issue of The  Journal of the American Medical Association.

SOURCES:

Kaklamani, V.G. TheJournal of the American Medical Association, Oct. 1, 2008; vol 300: pp 1523-1531.

Boris Pasche, MD, PhD, director, division of hematology/oncology; associate director for translational research, Comprehensive Cancer Center, University of Alabama at Birmingham.

Evadnie Rampersaud, PhD, research assistant professor, Miami Institute for Human Genomics, University of Miami Miller School of Medicine.

Sept. 30, 2008 -- Be extra careful driving on Nov. 4, because driving deaths tend to increase on U.S. presidential election days.

In fact, there are more traffic-related deaths on presidential election days than on the day of the Super Bowl, according to a report in tomorrow's edition of The Journal of the American Medical Association.

The report comes from Donald Redelmeier, MD, of Canada's University of Toronto and Robert Tibshirani, PhD, of Stanford University.

Using a national database, they counted the number of driving deaths on every presidential election day from 1976 (when Jimmy Carter was elected) to 2004 (when George W. Bush won).

For comparison, Redelmeier and Tibshirani also tracked the number of crash fatalities on the Tuesdays immediately before and after presidential election days.

An average of 158 people died in crashes per presidential election day, compared with 134 crash deaths per day on Tuesdays before and after presidential election days.

The typical victim was a young adult driving in a Southern state. Polling hours and whether a Democrat or Republican was elected didn't affect the trend.

Why would presidential election days be particularly deadly on the roads? There are more people on the roads, and if they're speeding, distracted, and not familiar with where they're going, those could all be factors, Redelmeier and Tibshirani say.

Their advice: Get-out-the-vote campaigners should emphasize basic driving safety tips, such as wearing your seatbelt, not speeding, abstaining from alcohol, and minimizing distractions.

The researchers' other suggestions include subsidized public transportation, voting centers within walking distances, tamper-proof remote voting, or more traffic enforcement on Election Day.

SOURCE:

Redelmeier, D. The Journal of the American Medical Association, Oct. 1, 2008; vol 300: pp 1518-1520.